Mild Transient Hypercapnia as a Novel Fear Conditioning Stimulus Allowing Re-Exposure during Sleep

Introduction:Studies suggest that sleep plays a role in traumatic memories and that treatment of sleep disorders may help alleviate symptoms of posttraumatic stress disorder. Fear-conditioning paradigms in rodents are used to investigate causal mechanisms of fear acquisition and the relationship between sleep and posttraumatic behaviors. We developed a novel conditioning stimulus (CS) that evoked fear and was subsequently used to study re-exposure to the CS during sleep.Methods:Experiment 1 assessed physiological responses to a conditioned stimulus (mild transient hypercapnia, mtHC; 3.0% CO2; n = 17)+footshock for the purpose of establishing a novel CS in male FVB/J mice. Responses to the novel CS were compared to tone+footshock (n = 18) and control groups of tone alone (n = 17) and mild transient hypercapnia alone (n = 10). A second proof of principle experiment re-exposed animals during sleep to mild transient hypercapnia or air (control) to study sleep processes related to the CS.Results:Footshock elicited a response of acute tachycardia (30-40 bpm) and increased plasma epinephrine. When tone predicted footshock it elicited mild hypertension (1-2 mmHg) and a three-fold increase in plasma epinephrine. When mtHC predicted footshock it also induced mild hypertension, but additionally elicited a conditioned bradycardia and a smaller increase in plasma epinephrine. The overall mean 24 hour sleep-wake profile was unaffected immediately after fear conditioning.Discussion:Our study demonstrates the efficacy of mtHC as a conditioning stimulus that is perceptible but innocuous (relative to tone) and applicable during sleep. This novel model will allow future studies to explore sleep-dependent mechanisms underlying maladaptive fear responses, as well as elucidate the moderators of the relationship between fear responses and sleep. © 2013 McDowell et al

Differences in pre-sleep activity and sleep location are associated with variability in daytime/nighttime sleep electrophysiology in the domestic dog

The domestic dog (Canis familiaris) is a promising animal model. Yet, the canine neuroscience literature is predominantly comprised of studies wherein (semi-)invasive methods and intensive training are used to study awake dog behavior. Given prior findings with humans and/or dogs, our goal was to assess, in 16 family dogs (1.5–7 years old; 10 males; 10 different breeds) the effects of pre-sleep activity and timing and location of sleep on sleep electrophysiology. All three factors had a main and/or interactive effect on sleep macrostructure. Following an active day, dogs slept more, were more likely to have an earlier drowsiness and NREM, and spent less time in drowsiness and more time in NREM and REM. Activity also had location- and time of day-specific effects. Time of day had main effects; at nighttime, dogs slept more and spent less time in drowsiness and awake after first drowsiness, and more time in NREM and in REM. Location had a main effect; when not at home, REM sleep following a first NREM was less likely. Findings are consistent with and extend prior human and dog data and have implications for the dog as an animal model and for informing future comparative research on sleep

Foot orthoses for flexible flatfeet in children and adults: a systematic review and meta-analysis of patient-reported outcomes

Background This systematic review and meta-analysis examined the effectiveness of orthoses for flexible flatfeet in terms of patient-reported outcomes in children and adults. Methods EMBASE, Medline (OvidSP), Web-of-Science, Scopus, CINAHL, Cochrane Central Register of Controlled Clinical Trials, i.e., Cochrane Central and Pubmed were searched to identify relevant studies since their inception up to February 2021. We included randomized controlled trials (RCT) and prospective studies in which patient reported outcomes at baseline and follow-up in an orthoses group were compared with a no orthoses or sham sole group. Methodological quality of the studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). A meta-analysis was performed where there were multiple studies with the same outcome measures, which was the case for the Visual Analogue Scale (VAS) for pain in adults. Results In total nine studies were included: four RCT in children (N = 353) and four RCT and one prospective study in adults (N = 268) were included. There was considerable heterogeneity between studies. A meta-analysis demonstrated that pain reduction between baseline and follow-up was significantly larger in the orthoses (N = 167) than in the control groups in adults (N = 157; - 4.76, 95% CI [- 9.46, - 0.06], p0.05). Conclusion Due to heterogeneity in study designs, we cannot conclude that foot orthoses are useful for flexible flatfoot in children and adults. However, based on the meta-analysis orthoses might be useful in decreasing pain in adults. The authors did not receive support from any organization for the submitted work

The role of patient characteristics and the effects of angiogenic therapies on the microvasculature of the meniscus: A systematic review

Background: Considerable interindividual variation in meniscal microvascularization has been reported. The purpose of this review was to identify which patient characteristics affect meniscal microvascularization and provide a structured overview of angiogenic ther-apies that influence meniscal neovascularization.Methods: A systematic literature search was undertaken using PubMed, Embase, Web of Science, Cochrane library and Emcare from inception to November 2021. Studies reporting on (1) Patient characteristics that affect meniscal microvascularization, or (2) Therapies that induce neovascularization in meniscal tissue were included. Studies were graded in quality using the Anatomical Quality Assessment (AQUA) tool. The study was registered with PROSPERO(ID:CRD42021242479).Results: Thirteen studies reported on patient characteristics and eleven on angiogenic ther-apies. The influence of Age, Degenerative knee, Gender, and Race was reported. Age is the most studied factor. The entire meniscus is vascularized around birth. With increasing age, vascularization decreases from the inner to the peripheral margin. Around 11 years, blood vessels are primarily located in the peripheral third of the menisci. There seems to be a fur-ther decrease in vascularization with increasing age in adults, yet conflicting literature exists. Degenerative changes of the knee also seem to influence meniscal vascularization, but evidence is limited. Angiogenic therapies to improve meniscal vascularization have only been studied in preclinical setting. The use of synovial flap transplantation, stem cell therapy, vascular endothelial growth factor, and angiogenin has shown promising results.Conclusion: To decrease failure rates of meniscal repair, a better understanding of patient -specific vascular anatomy is essential. Translational clinical research is needed to investi-gate the clinical value of angiogenic therapies.(c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Orthopaedics, Trauma Surgery and Rehabilitatio

Validity and reliability of the adapted Dutch version of the Brace Questionnaire (BrQ)

Background and purpose: The Brace Questionnaire (BrQ) is a disease-specific health-related quality of life (HRQOL) instrument for measuring perceived health status of scoliosis patients undergoing brace treatment. The purpose of this study is to evaluate the validity and reliability of a translated and culturally adapted Dutch version of the BrQ. Patients and methods: The original Greek BrQ was translated into Dutch and a cross-cultural adaptation and validation processes were conducted. Subsequently, 80 adolescent idiopathic scoliosis (AIS) patients undergoing active brace treatment were included from 4 scoliosis centers to evaluate the validity and reliability of the Dutch version of the BrQ. The questionnaire’s floor and ceiling effects, internal consistency, and test–retest reliability were assessed. Concurrent validity was evaluated by comparing the BrQ with the revised Scoliosis Research Society 22-item questionnaire (SRS-22r) scores. Results: The mean total BrQ score was 75.9 (standard deviation [SD] 11.3) and the mean domain scores varied between 3.4 (SD 0.9) and 4.2 (SD 0.7) for the domains “vitality” and “bodily pain,” respectively. There were no floor and ceiling effects for the total BrQ score. The BrQ showed satisfactory internal consistency in most subdomains with a Cronbach’s α ranging between 0.35 for the domain “general health perception” and 0.89 for the domain “self-esteem and aesthetics.” Excellent test–retest reproducibility was observed for the total BrQ score (ICC 0.91), and the BrQ was successfully validated against the SRS-22r. Conclusion: The translated and culturally adapted Dutch version of the BrQ is a valid and reliable HRQOL instrument for AIS patients undergoing brace treatment